脳卒中の分子生物学：神経細胞死と神経再生　　脳虚血におけるオリゴデンドロサイト細胞死とカスパーゼ

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  • Involvement of caspases in oligodendrocyte cell death under brain ischemia

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Oligodendrocytes (OLGs) are myelin forming cells in central nervous system and are thought to be vulnerable to hypoxia and ischemia. However, little is known about the detailed mechanism by which these insults induce oligodendrocyte death. Using the Cre-loxP system, we have established a transgenic mouse line that selectively expresses p35, a broad-spectrum caspase inhibitor, in OLGs. Under the hypoxic condition, cultured OLGs derived from wild-type mice exhibited significant up-regulation of caspase-11 and substantial activation of caspase-3, which led to cell loss.<BR>Expression of p35 or elimination of caspase-11 suppressed the caspase-3 activation and conferred significant protection against hypoxic injury. The expression of p35 in OLGs resulted in significant protection against ischemia-induced OLGs injury. Furthermore, the induction of caspase-11 was observed in the ischemic brain of wild-type mice and OLGs exhibited resistance to brain ischemia in mice deficient in caspase-11, suggesting that caspase-11 is critically implicated in the mechanism (s) underlying ischemia-induced OLG death.

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  • 脳卒中

    脳卒中 24 (4), 395-399, 2002

    一般社団法人 日本脳卒中学会

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